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Stem Cells: Introduction and
Prospects in Medicine
Professor Vassie Ware, 2012
Department of Biological Sciences
www.gothamgazette.com/.../stemcell/stem_cell.jpg
Overview
• What’s the Big Deal? A Historical Perspective and Future
Prospects in Regenerative Medicine
• Stem Cell Basics:
What are stem cells?
Where do stem cells come from?
Types of stem cells:
embryonic stem cells (ESCs)
adult-derived stem cells (ASCs)
induced pluripotent stem cells (iPSCs)
• Adult Stem Cell Advances in the News!
• Stem Cell Research Challenges
• Summary
Historical Perspective and
Prospects for Regenerative
Medicine
Historical Perspectives
• Major changes in cell-based therapies due to
advances in stem cell technologies
• Some stem cell therapies in existence for over 50
years. First successful bone marrow transplant done
in 1956 on leukemia patient. Bone marrow contains
adult-derived hematopoietic stem cells (able to
regenerate tissues similar to the specialized tissues in
which they are found).
• Embryonic stem cells, adult stem cells, and induced
pluripotent stem cells are believed to have great
potential for regenerative medicine.
From Solter, D. 2006 Nature Reviews Genetics 7, 319-327.
…
Development of
induced pluripotent
stem cells (iPSCs)
2007 Nobel Prize in Medicine
Mario R. Capecchi, Martin J. Evans and Oliver Smithies for their discoveries
of the principles for introducing specific gene modifications in mice by the use
of embryonic stem cells.
Modified from Solter, D. 2006 Nature Reviews Genetics 7, 319-327.
STEM CELL BASICS
I. What are stem cells?
Basic Characteristics of Stem Cells
Stem cell “niche” (neighborhood)
How do cells remain
self-renewing and
unspecialized?
Stem cells properties:
1. Capable of dividing and renewing
for long periods
2. Are unspecialized.
3. Give rise to specialized cells.
Adapted from Stem Cells and Cloning by Kelly A. Hogan;
http://stemcells.nih.gov/info/basics/basics2.asp
What are the
SIGNALS ???
Hormones
Growth factors
Small proteins
What distinguishes cell types from one another?
http://creationwiki.org/index.php/Stem_cell
Protein Profiles Differ in Different Cell Types
Figure from Stem Cells and Cloning by K.A. Hogan
Remember:
Unlike gametes (egg and sperm cells), all other
cells (somatic cells) have the same DNA content
and the same genes.
We can account for different protein patterns in
different types of cells:
the expression pattern of genes within
different types of cells is NOT identical.
Protein Profiles Differ in Different Cell Types
due to differential gene expression
Figure from Stem Cells and Cloning by K.A. Hogan
STEM CELL BASICS
II. Where do stem cells come from?
Different sources of stem cells during development
Adapted from Stem Cells and Cloning by K.A. Hogan
All stem cells are not alike!
• Some stem cells have more potential than others. POTENCY
describes this flexibility.
• Unipotent stem cells form only one type of specialized cell
type.
• Multipotent stem cells can form multiple types of cells and
tissue types.
• Pluripotent stem cells can form most or all cell types in the
adult.
• Totipotent stem cells can form all adult cell types as well as
the specialized tissues to support development of the embryo
(e.g., the placenta)
Isolation of Human Embryonic Stem Cells
First done by Dr.
James Thompson
and colleagues at
the University of
Wisconsin (1998).
Figure from Stem Cells and Cloning by K.A. Hogan
“Scientists Turn Human Skin Cells into
Stem Cells”
Induced pluripotent stem
cells (IPSCs or IP cells)
Adult Stem Cell Research in the News!
Selected News about Adult Stem Cells
“Scientists Find Way to Track Stem Cells in Brain”
(Science, November 2007)
“Stem Cells Restore Memory in Mice”
(Journal of Neuroscience, October 2007)
“Researchers Isolate Adult Stem Cells for First Time in Tendon”
(Nature Medicine, September 2007)
“ Stem Cells From Testes Produce Wide Range of Tissue Types”
(Nature, September 2007)
“First Neurons Created from ALS Patient’s Skin Cells”
(Science, July 2008 [online])
“Wisconsin team grows retina cells from skin-derived stem cells”
(PNAS, August 2009 [online])
“Mouse Study: Uterine Stem Cells Used To Treat Diabetes”
(Molecular Therapy, August 30, 2011)
“Scientists Discover New Class Of Stem Cell-Like Cells In Spinal Cord”
(PLoS ONE September 12, 2011)
“Long-Distance Growth and Connectivity of Neural Stem Cells after Severe
Spinal Cord Injury”
(Cell September 12, 2012)
Parkinson’s Disease (PD): Stem Cell Insights
Source cells
Differentiated Cell type
Host animal receiving
brain transplant
Results
Monkey ESCs
Dopamine-producing
neurons
Monkey model of PD
Diminished PD symptoms;
low survival rate of
transplanted cells
Human ESCs
Dopamine-producing
neurons
Rat model of PD
Significantly improved
muscle coordination;
tumor formation in brains
Human neural progenitor
cells from fetal tissue
engineered to express a
“survival factor”
N/A
Rat and monkey models of
PD
Improved symptoms of
PD; new dopamineproducing neurons
generated; effects not long
lasting
Adult human brain biopsy
cells
Neural progenitor cells
Mouse
New neurons generated
Mouse or human neural
ASCs
N/A
Mouse model of related
disease, Sandhoff’s
disease
Increased life span;
delayed loss of motor
function; no tumors
Human ESCs
Neural progenitor cells
Mouse model of
Sandhoff’s disease
Increased life span;
delayed loss of motor
function; no tumors
adapted from K.A. Hogan, Stem Cells and Cloning.
IMPACT :
• Understanding birth defects
• Possibility of generating patient-specific stem cell
lines to study the mechanism of different
diseases in the laboratory
• Creation of models for drug discovery and testing
the toxic effects of drugs
• Tissue engineering (e.g., use of progenitor cells to
make artificial bladders, retinas)
• To what degree do advances in adult stem cell
research alter the debate about the use of human
ES cells or not?
Stem Cell Therapy Challenges
• Safety challenges
Use of ESCs or differentiated cells derived from
ESCs for therapy:
- Considerations to avoid tumor
formation.
- Immune system challenges to avoid
rejection of foreign cells.
• Understanding the basic mechanisms that underlie
stem cell biology
• Social, ethical, political considerations for ESC
research
Summary:
•Stem cell therapies offer regenerative prospects for numerous
human diseases
•Stem cells are capable of renewal and differentiation.
•Stem cells are derived from numerous sources and have
different potency capacities.
•Adult stem cells (ASCs) have been detected in numerous tissues.
•Considerable ethical debate surrounds the use of embryonic stem cells.
Adult stem cells may offer similar prospects for therapy as do
ESCs, yet a complete understanding of stem cell applications
will require a basic understanding of differentiation and renewal
mechanisms in ASCs and ESCs as well.
Additional resources: http://stemcells.nih.gov/info/basics/
www.stemcellresearchnews.com
TAKE-HOME LESSON:
Ode to a Stem Cell, Part II©
by VCWare
There once was stem cell stuck in the ‘hood’
Dividing endlessly, but only wishing he could
Become something else, a skin cell, a hair cell, or some other type
But for weeks he sulked and uttered this gripe
“Why am I not needed?” to his friends he would say
Isn’t there a call for a specialist somewhere today?
Well, if you really want to leave to get a new start,
You must change your tune, for surely there is an art
To consider what signals you hear and choices you make.
Divide once more for the special journey you take.
Dare to be different, as you differentiate!
Rap performed by Isadore Carrie
Lehigh University, Class of 2013